6-125881163-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181782.5(NCOA7):​c.533T>A​(p.Val178Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NCOA7
NM_181782.5 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27
Variant links:
Genes affected
NCOA7 (HGNC:21081): (nuclear receptor coactivator 7) Enables nuclear receptor binding activity and nuclear receptor coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2349956).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NCOA7NM_181782.5 linkuse as main transcriptc.533T>A p.Val178Asp missense_variant 6/16 ENST00000392477.7 NP_861447.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NCOA7ENST00000392477.7 linkuse as main transcriptc.533T>A p.Val178Asp missense_variant 6/161 NM_181782.5 ENSP00000376269 Q8NI08-1
NCOA7ENST00000368357.7 linkuse as main transcriptc.533T>A p.Val178Asp missense_variant 7/171 ENSP00000357341 Q8NI08-1
NCOA7ENST00000229634.13 linkuse as main transcriptc.221T>A p.Val74Asp missense_variant 5/152 ENSP00000229634 Q8NI08-7
NCOA7ENST00000417494.5 linkuse as main transcriptc.533T>A p.Val178Asp missense_variant 6/62 ENSP00000406363

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461680
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000378
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 21, 2024The c.533T>A (p.V178D) alteration is located in exon 8 (coding exon 5) of the NCOA7 gene. This alteration results from a T to A substitution at nucleotide position 533, causing the valine (V) at amino acid position 178 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_addAF
Benign
-0.048
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
T;T;T;.
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
.;D;D;D
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.23
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.1
M;M;.;.
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-2.4
N;N;D;N
REVEL
Benign
0.099
Sift
Benign
0.056
T;T;T;T
Sift4G
Benign
0.062
T;T;D;T
Polyphen
0.89
P;P;.;.
Vest4
0.41
MutPred
0.21
Loss of glycosylation at S181 (P = 0.1098);Loss of glycosylation at S181 (P = 0.1098);Loss of glycosylation at S181 (P = 0.1098);.;
MVP
0.20
MPC
0.49
ClinPred
0.76
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.24
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1783793308; hg19: chr6-126202309; API